Accession Number : ADA322217

Title :   Role of Parathyroid Hormone-Related Protein in Breast Cancer Mediated Osteolysis.

Descriptive Note : Annual rept. 30 Sep 95-29 Sep 96,

Corporate Author : TEXAS UNIV AT SAN ANTONIO

Personal Author(s) : Guise, Theresa A.

PDF Url : ADA322217

Report Date : OCT 1996

Pagination or Media Count : 35

Abstract : This proposal is designed to investigate the role of PTHrP in breast cancer-mediated osteolysis. Observations in patients with bone metastases suggest that breast cancer cells in bone express PTHrP more frequently than in soft tissue sites of metastasis or in the primary tumor. Thus, the role of PTHrP in the causation of breast cancer metastases in bone was examined using human breast cancer cell lines. Four of eight breast cancer cell lines expressed PTHrP and one of these cell lines, MDA-MB-231, was studied in vivo. Mice inoculated with MDA-MB-231 cells developed osteolytic bone metastasis without hypercalcemia or increased plasma PTHrP concentrations. PTHrP concentrations in bone marrow plasma from femurs affected with osteolytic lesions were increased over corresponding plasma PTHrP concentrations. In a separate experiment, mice were treated with either a monoclonal antibody directed against PTHrP-(1-34), control IgG or nothing prior to tumor inoculation with MDA-MB-231 and twice per week for 26 days. Total area of osteolytic lesions was significantly lower in mice treated with PTHrP antibodies compared with mice receiving control IgG or no treatment. Histomorphometric analysis of bone revealed decreased osteoclast number per mm of tumor/bone interface, increased bone area as well as decreased tumor area in tumor-bearing animals treated with PTHrP antibodies compared with respective controls. These results indicate that PTHrP can cause local bone destruction in breast cancer metastatic to bone, even in the absence of hypercalcemia or increased circulating plasma concentrations of PTHrP.

Descriptors :   *PROTEINS, *PARATHYROID HORMONES, *BREAST CANCER, *OSTEOLYSIS, INTERFACES, NEOPLASMS, MICE, MONOCLONAL ANTIBODIES, INOCULATION, IN VIVO ANALYSIS, CELLS(BIOLOGY), BONE MARROW, LESIONS, HISTOLOGY, BLOOD PLASMA, LEGS, BONES, SOFT TISSUES, METASTASIS.

Subject Categories : Biochemistry
      Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE